Relapsed/Refractory Multiple Myeloma: Overview of Treatment Options

Switching their focus to the relapsed/refractory setting, experts from the Moffit Cancer Center consider second-line treatment options for patients with multiple myeloma.


Melissa Alsina, MD: We’re going to continue our discussion, now on the expanding treatment armamentarium in myeloma with novel therapies. We’re going to be focusing now on patients who have relapsed myeloma. As you know when patients have relapsed myeloma it’s different, when a patient has a first or second relapse vs a patient who has had multiple relapses, the treatments are different. Let’s first think about a patient who either had induction therapy, transplant, maintenance, or induction therapy and maintenance, and has that first relapse. What are the available treatment options for those patients, and how will you decide between one regimen and another? Rachid, do you want to start that discussion?

Rachid Baz, MD: Sure, I think we’re fortunate nowadays, we have a lot of agents at our disposal that are effective and don’t have a lot of toxicity. I think in early relapse, we’re likely to still encounter and see high response rates, even MRD [minimal residual disease] negativity, and this is unprecedented. I’ve been doing this for a long time, and it’s really great to see. Then we try to minimize toxicity, even considering patient convenience as a factor. A lot of times the question I ask myself in this setting is, what agents have they seen before? What are they refractory to, what are they experiencing or have experienced in terms of toxicity from before?

If you think about a patient who’s progressing on say lenalidomide maintenance, a daratumumab-based therapy or a CD28-based therapy makes a lot of sense. You can combine that with another IMiD [immunomodulatory drug], such as pomalidomide, or with a proteasome inhibitor, such as carfilzomib or bortezomib, for example. But I think the dara [daratumumab], pom [pomalidomide], or daratumumab, carfilzomib combination makes a lot of sense, and then we can try to tailor it based on risk. For example, is this a t(4;14) patient, a high-risk patient?

Or on the other hand, the type of relapse also can play a role, is it aggressive relapse or indolent relapse? But I think there is some room for tailoring the approach. One regimen is going to be a little more convenient than the next, the one that has an IMid vs if you have a proteasome inhibitor that will continue to have a long number of injections and an infusion that requires a cancer center to administer. These are some of the considerations we typically see, or we typically think about in the second-line setting. Obviously, we see other regimens that may apply to different situations, but I think that’s overwhelmingly common in these situations.

Melissa Alsina, MD: Yes, and what about if we’re talking specifically about the patient we just discussed before? He was a 74-year-old patient, transplant ineligible, you give induction therapy, and this patient had a translocation 11:14. Would you approach that patient differently?

Rachid Baz, MD: Yes, absolutely. I think venetoclax has beautiful responses in this patient population. Whether to use that in the second-line or the third-line setting is still a matter of debate, and also which agent to combine it with. You could think about a proteasome inhibitor [combination] with venetoclax, a CD38 antibody combo with venetoclax. We’ve published on this, and we’ve seen beautiful responses in that setting, so that’s definitely a personalized approach you can have, as well.

Ken Shain, MD: I was going to add to that for a second. Remember, venetoclax is again, for that 1 specific subtype. It’s truly the first kind of precision medicine we have in myeloma, again, although not FDA approved for myeloma, we know there are outstanding data in terms of response rates, even late relapse patients with venetoclax in translocation 11;14 patients, and even those who have high BCL2 expression, it’s target. So I think it’s something you have to keep in mind as a really good option, a safe option, and again, in combination for that subtype of patient. Then again, whether you use it in the second or third line, I think we all differ a bit. But I try to get it in there as soon as I can because I think the earlier you get it, the more bang for your buck you’re going to get with venetoclax. But again, precision medicine in myeloma is a cool concept, and it’s the first real agent we have that goes along those lines.

Melissa Alsina, MD: Yes, absolutely. Brandon, let’s talk only about the first relapse. When you’re treating a patient who has full relapse myeloma, clinical relapse, and at first relapse you decide to treat with one of the regimens Rachid and Ken were referring to, what is your goal of therapy?

Brandon Blue, MD: I think my goal, once someone relapses, is to try to get their disease under control, like it was before, as quickly as possible. The goal from upfront therapy is to get it down, drive it down, then maintain a response, but we know that myeloma is going to come back.It’s not an if, but a when. So I think when we see the disease relapse, we’ve got to make sure that’s still our goal, to get it right back down. We know that once the disease is under control, that decreases someone’s risk of having bone disease, having kidney disease, some of the terrible complications of myeloma. Because again, this is not curable cancer, so you want to try to do what you can to make sure someone’s quality of life is not impaired by the disease itself. The second thing is, you also want to make sure someone’s quality of life is not impaired by the treatment that you decide to give. Because you have to imagine that once someone relapses, they’re that much older than they were when they were first diagnosed. So now you have an older patient, but you still have to make sure you give them very effective therapy.

Melissa Alsina, MD: I definitely agree with you. I’ve been doing this for a long time too, as Rachid mentioned, and there was a time when we did not have these really good regimens for relapsed myeloma, and the approach toward relapsed myeloma was more like a palliative one. But now we have so many good regimens and combinations that probably you end up getting a patient back into remission. It’s like a start-over approach, right? It’s high, so I think it’s something to keep in mind. And if a patient has a clinical relapse, first relapse, I think we need to be aggressive and try to get the best response we possibly can in that patient population.

Transcript edited for clarity.

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